In the treatment of diabetes, insulin is presently administered by injection. Particularly, subcutaneous self-injection, a comparatively simple method, has been the major route of administration. However, patients are obliged to inject themselves before meal once to four times a day throughout their lives, and the discomfort accompanying injection is a major disadvantage of this method of treating diabetes.
Conversely, intranasal administration is known to be route that enables drugs to be rapidly absorbed post dosing. However, no insulin formulation for intranasal administration has been available for clinical use, due to poor absorbability and stability through/in the nasal cavity. Moreover, numerous preparations using absorption enhancers to improve the nasal absorbability of insulin have been impracticable because of irritation of the nasal mucosa.
JP-A-8-27031 presented a formulation for nasal absorption comprising a drug selected from a variety of drugs including physiologically active peptides such as insulin and calcitonin, and a polyvalent metallic compound as a carrier, which drug is uniformly dispersed on, adhered and binding to the carrier. According to this publication, it is suggested that, for example, the use of hydroxyapatite, calcium carbonate, calcium lactate, and magnesium stearate as carriers with an average particle diameter of 30-60 μm, enable insulin to be efficiently delivered into the systemic circulation. The application of hydroxyapatite with a particle diameter of 40-45 μm, as a carrier for nasal insulin absorption is comprehensively described in this publication, embodying account of an in vivo study that demonstrated the blood glucose level (blood-sugar level) after intranasal administration using the said formulation decreased in similar manner to that after subcutaneous administration.
The formulation for nasal absorption described in the above-mentioned JP-A-8-27031 has achieved a specific aim and is extremely beneficial. However, there is a great demand for a further optimized formulation (e.g. improved bioavailability) for nasal absorption.
Accordingly, the purpose of this invention is to provide a further optimized formulation for the nasal absorption of insulin that to enables high bioavailability.